Several suspected periodontopathic bacteria such as Porphyromonas gingivalis (Pg) are known to have enzymes capable of degrading human immunoglobulins G and A (IgG and IgA). The Fc fragments generated in this process may influence the pathogenesis of periodontal diseases by amplifying the inflammatory process. It is well established (primarily through work done in the lab of Dr. W.O. Weigle) that IgG and IgA Fc fragments are potent stimulators of T and B lymphocyte activation, which in turn leads to secretion of lymphokine mediators such as interleukin 6 (IL- 6). This research proposal seeks to test the capacities of Fc fragments generated by incubation of IgG1 and IgA1 myeloma proteins with Ig proteases derived from Pg to induce proliferation and Ig secretion by mouse splenic B cells, and IL-6 production by mouse splenic T cells. The effect of these Fc fragments on lymphokine production by Th1-like and Th2-like mouse splenic CD4+ cells obtained by fluorescence activated cell sorting will be studied using the RNase protection assay and the polymerase chain reaction. Finally, Fc fragment induction of cell-surface activation markers and early intracellular activation events such as calcium mobilization and RNA synthesis will be studied in human peripheral blood lymphocytes using flow cytometry. These studies will provide new information about how bacteria like Pg induce periodontal disease, as well as new knowledge about the immunoregulation of T and B lymphocytes.